ObjectiveTo observe the effects of Yangjing Zhongyutang （YJZYT） on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor gamma coactivator-1alpha （PGC-1α） signaling pathway in cyclophosphamide （CTX）-induced rats with diminished ovarian reserve （DOR）， and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group （n=7） and a model group （n=35）. Rats in the model group received a single intraperitoneal injection of CTX （90 mg·kg^-1） to establish the DOR model. After modeling， estrous cycles were monitored for 7 consecutive days， and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling， rats were divided into groups for intervention： estradiol valerate group （0.09 mg·kg^-1）， and YJZYT high-， medium-， and low-dose groups （19.98， 9.99， 5.00 g·kg^-1）. The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state， body weight， and ovarian wet weight of rats were observed and recorded， and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， anti-Müllerian hormone （AMH）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Hematoxylin-eosin （HE） staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species （ROS） expression levels. Colorimetric assays were employed to measure adenosine triphosphate （ATP） and malondialdehyde （MDA） content in ovarian tissues. Quantitative Real-time polymerase chain reaction （Real-time PCR） was used to detect mitochondrial DNA （mtDNA） copy number and the mRNA expression levels of key genes including SIRT1， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM）. Western blot was performed to detect the protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM. ResultsCompared with the blank group， rats in the model group exhibited disrupted estrous cycles， obviously reduced body weight， and decreased ovarian index （P<0.05）. Ovarian histopathology revealed cortical thinning， loose structure， and a significant reduction in both primordial and growing follicles （P<0.01）. Serum FSH and LH levels were significantly elevated （P<0.01）， while E₂ and AMH levels were obviously reduced （P<0.05， P<0.01）. ATP content and mtDNA copy number decreased in ovarian tissue （P<0.01）， ROS expression increased， MDA levels rose， while SOD and GSH-Px activities obviously decreased （P<0.05， P<0.01）， mRNA and protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM were obviously downregulated （P<0.05， P<0.01）. After treatment， compared with the model group， body weight and ovarian index obviously recovered in rats administered various doses of YJZYT （P<0.05）， serum E₂ and AMH levels increased， while FSH and LH levels obviously decreased （P<0.05， P<0.01）， ovarian tissue ATP content and mtDNA copy number were up-regulated， ROS and MDA levels decreased， and antioxidant enzymes SOD and GSH-Px activity obviously increased （P<0.05， P<0.01）， Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group （P<0.05， P<0.01）， HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups， with a obviously increase in the number of primordial and growing follicles （P<0.05， P<0.01）. Granulosa cells were neatly arranged， indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway， promoting mitochondrial biogenesis， enhancing mitochondrial function， and alleviating oxidative stress damage.

Objective: To explore the effects of personality and sleep quality with psychological distress of junior and senior high school stduents, so as to provide a reference basis for precise interventions of junior and senior high school students mental health. Methods: In October 2023, a convenience sampling method was used to select 9 034 students aged 12-17 from Shiyan City as the study subjects. The Pittsburgh Sleep Quality Index (PSQI) and Kessler Psychological Distress Scale (K10) were used to collect information on sleep quality and psychological distress of junior and senior high school stduents. Between group comparison was conducted by using t-test and Chi-square test. Generalized linear models were employed to analyze the interaction and joint effects of personality and sleep quality on psychological distress. Results: The generalized linear model analysis showed that the interaction between personality and sleep quality on psychological distress was statistically significant of junior and senior high school students(effect size=0.80, P <0.01). The general linear model analysis indicated that, after adjusting for variables such as age, gender, screen time, and daily sitting time with the extroverted and good sleep quality group as the reference, the introverted and poor sleep quality group had the largest mean difference in psychological distress scores (difference=0.51, P <0.05). When stratified by sleep quality, psychological distress scores were higher in the introverted and neutral personality groups with both poor and good sleep quality compared to the extroverted group (poor sleep quality: introverted difference=3.71, neutral difference=1.14; good sleep quality: introverted difference=2.23, neutral difference=0.57, all P < 0.05). When stratified by personality, psychological distress scores were higher in the poor sleep quality groups for introverted, neutral, and extroverted individuals compared to their good sleep quality counterparts (differences=8.66, 7.83, 7.34, all P < 0.05 ). Conclusions Personality and sleep quality have interactive and joint effects on psychological distress of junior and senior high school stduents. Personalized psychological interventions should be developed based on personality and sleep quality.

Ephedra can improve chronic obstructive pulmonary disease (COPD). Pseudoephedrine (PSE) is a main active ingredients of ephedra. It has anti-inflammatory pharmacological properties. Its effect on COPD and its possible mechanism have not been elucidated. The COPD rat model was constructed by systemic cigarette smoke exposure combined with lipopolysaccharide (LPS) tracheal instillation. BEAS-2B cells were treated using cigarette smoke extract; PSE was administered for treatment. The senescence level of rat lung tissue and bronchial epithelial cells was evaluated through staining, immunofluorescence and western blot.The mitochondrial damage of rats and BEAS-2B cells was detected by transmission electron microscopy, JC-1 probe, MitoSOX Red probe and kits. In addition, the lung function indexes of rats were detected by animal lung function analysis system. Hematoxylin and eosin (HE) staining analyzed the pathological damage. Enzyme-linked immunosorbent assay (ELISA), kit and immunohistochemistry were used to evaluate inflammation and oxidative stress. Western blot detected phosphoinositide 3-kinase/ protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) axis protein. PSE significantly reduced senescent cells, apoptosis rate and P21 level in rat lung tissue and BEAS-2B cells, significantly increased the levels of zonula occludens-1 (ZO-1) and adenosine triphosphate (ATP), restored mitochondrial structure, and visible mitochondrial cristae. It also inhibited reactive oxygen species (ROS) levels and mitochondrial excessive fission. PSE also significantly improved lung function in rats, increased mean alveolar number (MAN), reduced pro-inflammatory factors, and increased superoxide dismutase (SOD) levels. PSE markedly suppressed p-p85, p-AKT and p-mTOR protein expressions. In addition, the PI3K/AKT agonist 740Y-P weakened the effect of PSE on improving COPD. PSE inhibited PI3K/AKT/mTOR axis, improved lung tissue senescence, mitochondrial dysfunction and pathological damage, and reduced airway inflammation and oxidative stress damage, thereby alleviating COPD.

Objective To investigate the expression of six-transmembrane epithelial antigen of prostate 4 (STEAP4) in prostate cancer (PCa), explore its correlation with the infiltration of regulatory T cells (Tregs) and CD8+T cells within the tumor-infiltrating T lymphocyte population, and to predict the potential role of STEAP4 in promoting PCa progression. Methods The clinicopathological data and tumor tissue specimens were collected from 90 PCa patients undergoing radical prostatectomy at our hospital during Jan.2018 and Dec.2024.The protein expressions of STEAP4, forkhead box transcription factor P3 (FoxP3), and CD8+T cells in tumor tissues were detected with immunohistochemistry.The correlation between STEAP4 expression and the infiltration of Tregs (FoxP3 T cells), CD8+T cells and clinicopathological characteristics was analyzed.The relationship between STEAP4 expression and prognosis was evaluated with Kaplan-Meier survival curves. Results STEAP4 expression was significantly higher in PCa tissues than in adjacent benign tissues (P＜0.001).STEAP4 expression was significantly associated with serum total prostate-specific antigen (tPSA) level, seminal vesicle invasion, extraprostatic extension, International Society of Urological Pathology (ISUP) grading, and pathological T stage (all P＜0.05).The mean infiltration density of Tregs (FoxP3 T cells) in PCa tissues was significantly higher than that in adjacent benign tissues[ (11.09±5.05) cells/HPF vs. (3.92±1.59) cells/HPF, P＜0.001], while the mean infiltration density of CD8+T cells was significantly lower[ (6.07±2.90) cells/HPF vs. (27.23±6.75) cells/HPF, P＜0.001].In PCa tissues, STEAP4 expression showed a significant positive correlation with Treg (FoxP3 T cells) infiltration density (r_s=0.472, P＜0.001) and a significant negative correlation with CD8+T-cell infiltration density (r_s=-0.495, P＜0.001).Kaplan-Meier survival curves indicated that high STEAP4 expression group and low STEAP4 expression group in PCa patients was not correlated with overall survival (OS) or recurrence-free survival (P=0.562, 0.346). Conclusion STEAP4 is highly expressed in PCa tissues, and its expression is closely associated with tumor-infiltrating lymphocytes, particularly Tregs and CD8+T cells, suggesting that STEAP4 may cooperate with Tregs and CD8+T cells to regulate the tumor microenvironment, thereby promoting PCa progression.

BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.

BACKGROUND:The extracellular matrix is a complex network structure,which not only builds physical support for tissue cells,but also plays an important regulatory role in cell survival,proliferation,and death.Abnormal changes in the biochemical and biomechanical properties of the extracellular matrix can significantly affect the proliferation,migration,immune evasion,and treatment resistance of tumor cells.Stiffness is an important mechanical property of the extracellular matrix,and abnormalities in matrix stiffness are closely related to tumor progression.OBJECTIVE:By reviewing the mechanism of extracellular matrix sclerosis,the impact of high stiffness matrix on tumor progression,and the latest research progress in the treatment of cancer based on reducing matrix stiffness,to deeply understand the mechanical properties of the extracellular matrix,improve the understanding of the complex mechanism of tumor progression,and provide new ideas and directions for tumor treatment.METHODS:"Extracellular matrix function,extracellular matrix stiffness,collagen deposition cross-linking,extracellular matrix stiffness therapy,immunotherapy"were used as the search terms in Chinese and English.Relevant literature published from January 2016 to June 2024 was searched in CNKI,PubMed,and WanFang databases,and 80 articles were finally included for review.RESULTS AND CONCLUSION:(1)Deposition and excessive cross-linking of collagen and elastin in the extracellular matrix leads to matrix remodeling,which in turn increases matrix stiffness.This sclerosis activates pro-cancer signaling pathways such as cyclin-D1,Rho/ROCK,p-PXN-Rac1-YAP,and STAT3/p-STAT3,promotes malignant behaviors such as cancer cell proliferation,metastasis,tumor microangiogenesis and immune escape,and accelerates tumor progression.(2)Reducing the deposition and cross-linking of matrix proteins can reduce matrix stiffness,which cannot only inhibit the activation of multiple cancer-promoting signaling pathways,but also enhance the penetration and delivery of drugs at tumor sites,which is a new strategy for cancer treatment.(3)At present,drugs based on matrix degradation to reduce tumor stiffness are under development,and a few drugs have entered the clinical trial stage,which are expected to provide a new powerful weapon for tumor treatment.

Objective To investigate the efficacy of Xingpi Huazhuo Prescription in treating pre-diabetic patients with phlegm-damp constitution and its impacts on blood glucose levels and renal func-tion indicators.Methods A total of 104 pre-diabetic patients with phlegm-damp constitution admitted to the hospital between January 2021 and December 2023 were selected and randomly divided into west-ern medicine group(n=52)and combined group(n=52)using a random number table method.The western medicine group received metformin treatment,while the combined group received metformin combined with Xingpi Huazhuo Prescription.Clinical efficacy was recorded after 3 months of treatment,and blood glucose indexes such as[fasting blood glucose(FPG),glycated hemoglobin(HbA1c),and 2-h plasma glucose(2 hPG)]levels,lipid indicators[triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)],and renal function indicators[serum creatinine(Scr),urea nitrogen(BUN),β2-microglobulin(β2-MG)]were compared before and after 3 months of treatment.Results After 3 months of treatment,the total clinical effectiveness in the combined group was higher than that in the western medicine group(P＜0.05).After 3 months of treatment,the levels of FPG,HbA1c,and 2 hPG decreased in both groups,and the combined group showed lower levels than the western medicine group(P＜0.05).After 3 months of treatment,the levels of TG,TC,and LDL-C decreased in both groups compared with before treatment,and the combined group showed lower levels than the western medicine group(P＜0.05);the levels of HDL-C increased in both groups,and the combined group showed higher levels than the western medicine group(P＜0.05).After 3 months of treatment,the levels of Scr,BUN,and β2-MG decreased in both groups,with the combined group showing lower levels than the western medicine group(P＜0.05).Conclusion In pre-diabetic patients with phlegm-damp con-stitution,metformin combined with Xingpi Huazhuo Prescription can effectively improve blood glu-cose levels and exert renal protective effects.

MicroRNA(miRNA),an important type of non-coding RNAs existing widely in viruses and eukaryotes,regulate gene expression at transcriptional and post-transcriptional levels.Recent studies have demonstrated that plant miRNAs could enter microorganisms,animals and human bodies to affect their physiological and pathological processes by cross-kingdom regulation of gene expression.This review summarized the current knowledge of cross-kingdom regulation of gene expression by plant miRNAs,introduced the research progress in intervention of human diseases with plant miRNAs,including anti-virus,anti-tumor,anti-inflammation,immune regulation,anti-fatigue,anti-fibrosis,vascular protection,nerve protection,etc.,and analyzed the reasons why plant miRNAs remain stable in vivo and in vitro and the underlying mechanisms how they regulate human gene expression.Furthermore,the impact of cross-kingdom regulation by plant miRNAs on exploring new active ingredients of traditional Chinese herbs and elucidating their pharmacology were evaluated.Finally,"constructing the complex regulatory network of traditional Chinese medicine miRNAs in human body"and"exploring new mechanisms of gene expression regulation by traditional Chinese medicine miRNAs"were pointed out,which were two scientific problems worthy of further investigation.

Objective:To analyze the clinical characteristics and nutritional treatment of malnutrition in infants with botulism.Methods:A retrospective analysis was conducted on 25 infant botulism patients admitted to Beijing Children's Hospital Affiliated to Capital Medical University，from May 1，2019 to October 31，2024.The nutritional risk and malnutrition incidence were assessed，nutritional therapy methods，formulations，tolerance status, energy intake rate, secondary infections and prognosis were analyzed.Results:A total of 25 pediatric patients were included, 19 males and 6 females, with a median age of 5(4,6) months. Twenty-five cases (100%) showed reduced food intake, with a weight of 7.3 (7.0, 9.0) kg upon admission. Twenty-four cases (96%) were assessed as high-risk for nutrition screening, and one case was diagnosed with malnutrition. Twenty-four cases (96%) received nasogastric tube feeding, with an early enteral nutrition implementation rate of 84% (21 cases) and intermittent infusion in 25 cases (100%). Fourteen cases used whole protein formula milk,eight cases used hydrolyzed protein formula milk and three cases were given 5% sugar solution. Nine cases were treated with intravenous nutrition, with a duration of 9 (5, 12) days. Five cases (20%) developed enteral feeding intolerance, and all five cases had secondary infections and were treated with parenteral nutrition. All 25 patients had good prognosis. At discharge, 17 cases (68%) were fed orally, and eight cases (32%) were fed through nasogastric tubes, with a median weight of 7.5 (7.0, 9.0) kg. Fifteen patients (60%) had weight gain, and the nutritional screening assessment was all low-risk.Conclusion:Infants with botulism are mostly in a state of high nutritional risk when they are admitted to hospital. Early enteral nutrition through a gastric tube has a high implementation rate. Some children may experience feeding intolerance,combined with timely use of parenteral nutrition replacement and symptomatic treatment can improve prognosis.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*